Department of Chemistry, Rice University, Houston, TX 77005, USA.
Department of Physics and Astronomy, Center for Theoretical Biological Physics, Rice University, Houston, TX 77005, USA.
J R Soc Interface. 2018 Jan;15(138). doi: 10.1098/rsif.2017.0809.
Gene regulatory networks must relay information from extracellular signals to downstream genes in an efficient, timely and coherent manner. Many complex functional tasks such as the immune response require system-wide broadcasting of information not to one but to many genes carrying out distinct functions whose dynamical binding and unbinding characteristics are widely distributed. In such broadcasting networks, the intended target sites are also often dwarfed in number by the even more numerous non-functional binding sites. Taking the genetic regulatory network of NFB as an exemplary system we explore the impact of having numerous distributed sites on the stochastic dynamics of oscillatory broadcasting genetic networks pointing out how resonances in binding cycles control the network's specificity and performance. We also show that active kinetic regulation of binding and unbinding through molecular stripping of DNA bound transcription factors can lead to a higher coherence of gene-co-expression and synchronous clearance.
基因调控网络必须以高效、及时和连贯的方式将信息从细胞外信号传递到下游基因。许多复杂的功能任务，如免疫反应，需要系统范围的信息广播，而不是一个基因，而是许多执行不同功能的基因，其动态结合和解离特征分布广泛。在这种广播网络中，目标结合位点的数量通常也远远少于数量更多的非功能结合位点。我们以 NFKB 的遗传调控网络为例系统地研究了具有众多分布式结合位点对振荡广播遗传网络随机动力学的影响，指出结合循环中的共振如何控制网络的特异性和性能。我们还表明，通过分子去除 DNA 结合转录因子来主动调节结合和解离的动力学，可以提高基因共表达的一致性和同步清除。
